The release of norepinephrine (NE) by the renal sympathetic nerves increases renin release by stimulating Beta-adrenergic receptors located on the granular juxtaglomerular cells of the kidney, and many vasodepressor agents (including Alpha-adrenergic antagonists such as phentolamine and phenoxybenzamine which possess significant activity at the postjuctional Alpha1-adrenergic receptors of the vasculature) stimulate renin release by reflex activation, vai the carotid baroreflex, of the renal sympathetic nerves. The stimulation by NE of prejunctional Alpha2-adrenergic receptors inhibits the release of NE by the sympathetic neuron, and blockade of these receptors by Alpha2-adrenergic antagonists results in a greater release of NE at low frequencies of nerve activity. The Alpha2-adrenergic antagonist possess little activity at the postjunctional Alpha1-adrenergic receptor of the vasculature and therefore do not lower blood pressure. These experiments are designed to test the hypothesis that blockade of these prejunctional Alpha-adrenergic receptors with the preferential Alpha2-adrenergic antagonists yohimbine, rauwolscine, piteroxane and RS 21361 will increase renin release by increasing noradrenergic neurotransmission in the kidney in the absence of hypotensive activation of the carotid baroreflex. Using conscious rats, the chronology and dose-response relationships of the increase in renin release and the changes in mean arterial pressure (MAP), heart rate and plasma NE and epinephrine (Epi) concentrations caused by these drugs will be characterized. In addition, the ability of propranolol, indomethancin, meclofenamate and salt loading and salt depletion to alter the stimulation of renin release caused by these Alpha2-adrenergic antagonists will be studied. The effect of these Alpha2-adrenergis antagonists on the release of renin and NE caused by stimulation of the renal nerves of the isolated perfused rat kidney will be examined. The ability of these Alpha2-adrenergic antagonists to alter the neurally-dependent renin released caused by hydralazine, prazosin and physostigmine and the neurally-dependent release caused by chlorisondamine and insulin will be examined. Parallel measurements of MAP, heart rate and plasma NE and Api content will be made in the latter experiments. These studies will serve to delineate the of prejunctional Alpha-adrenergic receptors in the neural control of renin release. Th date, no one has studied the role of prejunctional Alpha2-adrenergic receptors in the neural control of renin release.